COMPARATIVE BACTERICIDAL ACTIVITY OF CEFTAZIDIME AGAINST ISOLATES OF PSEUDOMONAS-AERUGINOSA AS ASSESSED IN AN IN-VITRO PHARMACODYNAMIC MODEL VERSUS THE TRADITIONAL TIME-KILL METHOD

Bactericidal activity, historically assessed by in vitro tests which e mploy fixed drug concentrations, may also be evaluated in in vitro pha rmacodynamic models in which in vivo pharmacokinetics and bacterial gr owth conditions can be simulated, However, systematic comparisons betw een the two methods are lacking, We evaluated the bactericidal activit ies of ceftazidime, at two different concentration/MIC ratios (C/MICs) , against 10 clinical isolates of Pseudomonas aeruginosa in a two-comp artment model with continuous-infusion conditions and a 2-h half-life. These values were compared to those determined by traditional 24-h ti me-kill (TTK) methods at the same C/MICs, Bactericidal activities were compared by using area under the colony count-time curves, Antibiotic exposure (area under the drug concentration-time curve) was also eval uated, Although bactericidal activity appeared greater by the TTK meth od (P = 0.05), when it was normalized for drug exposure, these differe nces disappeared (P = 0.2), This disparity was likely due to differenc es in drug exposure in the TTK method and in the peripheral compartmen t of the model (site of bacteria) over the first 8 h of the experiment , during which the antibiotic accumulated to target concentrations, Th is suggests that the bactericidal effects with constant antibiotic con centrations are similar in the two methods; however, this may not hold true with fluctuating drug concentrations, Further, results from the pharmacodynamic model may theoretically be more relevant, as in vivo p harmacokinetics and bacterial growth conditions can be more faithfully simulated.